Modulatory Effects of Levodopa on Cerebellar Connectivity in Parkinson’s Disease

• Published in: Cerebellum (London, England) Vol. 18; no. 2; pp. 212 - 224
• Main Authors: Mueller, Karsten, Jech, Robert, Ballarini, Tommaso, Holiga, Štefan, Růžička, Filip, Piecha, Fabian A., Möller, Harald E., Vymazal, Josef, Růžička, Evžen, Schroeter, Matthias L.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.04.2019; Springer Nature B.V
• Subjects: Adult; Aged; Antiparkinson Agents - therapeutic use; Biomedical and Life Sciences; Biomedicine; Brain mapping; Brain Mapping - methods; Brain stem; Cerebellum; Cerebellum - diagnostic imaging; Cerebellum - drug effects; Cerebellum - physiopathology; Dopamine receptors; Dyskinesia; Female; Functional magnetic resonance imaging; Globus pallidus; Humans; Levodopa; Levodopa - therapeutic use; Magnetic Resonance Imaging - methods; Male; Middle Aged; Motor task performance; Movement disorders; Neural networks; Neural Pathways - diagnostic imaging; Neural Pathways - drug effects; Neural Pathways - physiopathology; Neurobiology; Neurodegenerative diseases; Neuroimaging; Neurology; Neurosciences; Original Paper; Parkinson Disease - diagnostic imaging; Parkinson Disease - drug therapy; Parkinson Disease - physiopathology; Parkinson's disease; Patients; Putamen; Rest; Thalamus; Therapeutic applications; Functional connectivity; Cerebellum; L-dopa; Brain connectivity; Resting-state magnetic resonance imaging; Eigenvector centrality; Brainstem; Nexopathy; Dopaminergic treatment; Levodopa; Parkinson’s disease; Cerebellar networks
• ISSN: 1473-4222; 1473-4230
• DOI: 10.1007/s12311-018-0981-y

Levodopa has been the mainstay of symptomatic therapy for Parkinson’s disease (PD) for the last five decades. However, it is associated with the development of motor fluctuations and dyskinesia, in particular after several years of treatment. The aim of this study was to shed light on the acute brain functional reorganization in response to a single levodopa dose. Functional magnetic resonance imaging (fMRI) was performed after an overnight withdrawal of dopaminergic treatment and 1 h after a single dose of 250 mg levodopa in a group of 24 PD patients. Eigenvector centrality was calculated in both treatment states using resting-state fMRI. This offers a new data-driven and parameter-free approach, similar to Google’s PageRank algorithm, revealing brain connectivity alterations due to the effect of levodopa treatment. In all PD patients, levodopa treatment led to an improvement of clinical symptoms as measured with the Unified Parkinson’s Disease Rating Scale motor score (UPDRS-III). This therapeutic effect was accompanied with a major connectivity increase between cerebellar brain regions and subcortical areas of the motor system such as the thalamus, putamen, globus pallidus, and brainstem. The degree of interconnectedness of cerebellar regions correlated with the improvement of clinical symptoms due to the administration of levodopa. We observed significant functional cerebellar connectivity reorganization immediately after a single levodopa dose in PD patients. Enhanced general connectivity (eigenvector centrality) was associated with better motor performance as assessed by UPDRS-III score. This underlines the importance of considering cerebellar networks as therapeutic targets in PD.